Thebroad,long-?termgoalofthisprojectisconsistent,standardizeddiagnostictestingofsurgical specimensbyimmunohistochemistry(IHC).Themethodstoachievethisgoalarewellunderstoodinthe fieldofclinicallaboratorytesting:(1)standardizationofreagentsandprotocols,(2)automationto reducehumanerrors,and(3)theuseofstandardizedcontrolstoprovidetestperformancefeedback. Overthelasttwodecades,thefirsttwoofthesethreemethodswereimplementedforIHCtesting.This grantprojectfocusesonthethird-?-?standardizedIHCcontrols.Currentpracticeteachesnon- standardizedcontrols.Eachhistopathologylabtypicallyprocurestestcontrolsfromleftovertissue samplesinitsownparaffinblockarchives.Thisisastrikinglydifferentpracticefromclinicalblood laboratories,wherestandardizedandvalidatedcontrolsareproducedinlargequantitiesandsold throughcommercialvendors. Wehavedevelopedaninnovativetechnicalsolution,summarizedinaseriesofpublishedjournal articles.Overthelast2yearsandwithNCIfunding,ourbreastcancerIHControlsTMpanelforHER-?2,ER, andPRtestsrecentlyenteredclinicaltestingandwillbesubmittedforregulatoryclearancethisyear (2016). ThisDirect-?to-?PhaseIIproposaladdressesclinicalIHClaboratorypracticebeyondbreastcancer testing.WewillexpandtheIHControlsTMproductportfolio,from3analytes(HER-?2,ER,&PR)to30.The newIHControlsTMpanelscomprisetheGeneralPathology,Melanoma,LungCancer,andHematopathology testportfolios.Thisten-?foldexpansionisfeasiblewithfundingfromasinglePhaseIIgrantbecause:(a) wehavealreadyworkedoutthenuancesofproductdesign,manufactureundercGMP,andtesting,and (b)theadditionalanalyteswillmostlybeclassIproducts.TheSpecificAimsofthisproposalare:(1) creationofthenewIHControlsTMpanels,(2)analyticalvalidation,includingtestingforsensitivity, specificity,productstability,andmanufacturingreproducibility,and(3)clinicalvalidation,including testingforprecision,referenceinterval(expectedlevelofstaining),andlimitofdetection. Theapplicantgroupcomprisesabroad,multi-?disciplinaryteam,includingtheMDPR&Dteam, statisticalsupportfromtheTuftsClinical&TranslationalScienceInstitute(CTSI),surgicalpathologists, andconsultantsforregulatoryaffairs,qualitysystems,andIHCcommercialoperations.Converting clinicallaboratoriesfromhomebrewtostandardizedcontrolswillbeatransformativechange.